Tremor in multiple sclerosis is associated with cerebello-thalamic pathology.

Tremor in people with multiple sclerosis (MS) is a frequent and debilitating symptom with a relatively poorly understood pathophysiology. To determine the relationship between clinical tremor severity and structural magnetic resonance imaging parameters. Eleven patients with clinically definite MS and right-sided upper limb tremor were studied. Tremor severity was assessed using the Bain score (overall severity, writing, and Archimedes spiral drawing). Cerebellar dysfunction was assessed using the Scale for the Assessment and Rating of Ataxia. Dystonia was assessed using the Global Dystonia Scale adapted for upper limb. For all subjects, volume was calculated for the thalamus from T1-weighted volumetric scans using Freesurfer. Superior cerebellar peduncle (SCP) cross-sectional areas were measured manually. The presence of lesions was visually determined and the lesion volumes were calculated by the lesion growth algorithm as implemented in the Lesion Segmentation Toolbox. Right thalamic volume negatively correlated with Bain tremor severity score (ρ = - 0.65, p = 0.03). Left thalamic volume negatively correlated with general Bain tremor severity score (ρ = - 0.65, p = 0.03) and the Bain writing score (ρ = - 0.65, p = 0.03). Right SCP area negatively correlated with Bain writing score (ρ = - 0.69, p = 0.02). Finally, Bain Archimedes score was significantly higher in patients with lesions in the contralateral thalamus. Whole brain lesion load showed no relationship with tremor severity. These results implicate degeneration of key structures within the cerebello-thalamic pathway as pathological substrates for tremor in MS patients.

Very early initiation of chemical venous thromboembolism prophylaxis after blunt solid organ injury is safe.

BACKGROUND: The optimal timing of initiating low-molecular weight heparin (LMWH) in patients who have undergone nonoperative management (NOM) of blunt solid organ injuries (SOIs) remains controversial. We describe the safety of early initiation of chemical venous thromboembolism (VTE) prophylaxis among patients undergoing NOM of blunt SOIs. METHODS: We retrospectively studied severely injured adults who sustained blunt SOI without significant intracranial hemorrhage and underwent an initial NOM at a Canadian lead trauma hospital between 2010 and 2014. Safety was assessed based on failure of NOM, defined as the need for operative intervention, in patients who received early (< 48 h) or late LMWH (≥ 48 h, or early discharge [< 72 h] without LMWH). RESULTS: We included 162 patients in our analysis. Most were men (69%), and the average age was 42 ± 18 years. The median injury severity score was 17, and splenic injuries were most common (97 [60%], median grade 2), followed by liver (57 [35%], median grade 2) and kidney injuries (31 [19%], median grade 1). Combined injuries were present in 14% of patients. A total of 78 (48%) patients received early LMWH, while 84 (52%) received late LMWH. The groups differed only in percent of high-grade splenic injury (14% v. 32%). Overall 2% of patients failed NOM, none after receiving LMWH. Semielective angiography was performed in 23 (14%) patients. The overall rate of confirmed VTE on imaging was 1.9%. CONCLUSION: Early initiation of medical thromboembolic prophylaxis appears safe in select patients with isolated SOI following blunt trauma. A prospective multicentre study is warranted.

A novel literature-based approach to identify genetic and molecular predictors of survival in glioblastoma multiforme: Analysis of 14,678 patients using systematic review and meta-analytical tools.

Glioblastoma multiforme (GBM) has a poor prognosis despite maximal multimodal therapy. Biomarkers of relevance to prognosis which may also identify treatment targets are needed. A few hundred genetic and molecular predictors have been implicated in the literature, however with the exception of IDH1 and O6-MGMT, there is uncertainty regarding their true prognostic relevance. This study analyses reported genetic and molecular predictors of prognosis in GBM. For each, its relationship with univariate overall survival in adults with GBM is described. A systematic search of MEDLINE (1998-July 2010) was performed. Eligible papers studied the effect of any genetic or molecular marker on univariate overall survival in adult patients with histologically diagnosed GBM. Primary outcomes were median survival difference in months and univariate hazard ratios. Analyses included converting 126 Kaplan-Meier curves and 27 raw data sets into primary outcomes. Seventy-four random effects meta-analyses were performed on 39 unique genetic or molecular factors. Objective criteria were designed to classify factors into the categories of clearly prognostic, weakly prognostic, non-prognostic and promising. Included were 304 publications and 174 studies involving 14,678 unique patients from 33 countries. We identified 422 reported genetic and molecular predictors, of which 52 had ⩾2 studies. IDH1 mutation and O6-MGMT were classified as clearly prognostic, validating the methodology. High Ki-67/MIB-1 and loss of heterozygosity of chromosome 10/10q were classified as weakly prognostic. Four factors were classified as non-prognostic and 13 factors were classified as promising and worthy of additional investigation. Funnel plot analysis did not identify any evidence of publication bias. This study demonstrates a novel literature and meta-analytical based approach to maximise the value that can be derived from the plethora of literature reports of molecular and genetic factors in GBM. Caution is advised in over-interpreting the results due to study limitations. Further research to develop this methodology and improvements in study reporting are suggested.

The Shock Index: is it ready for primetime?

The rapid and accurate prediction of the need for massive transfusion in bleeding trauma patients remains a challenge. Various models have been proposed to anticipate massive transfusion with variable success. The current study by Mutschler and colleagues proposes four classes of shock as defined by the Shock Index and examines its ability to predict the need for massive transfusion. This model demonstrates promise as a practical tool in acute decision-making for transfusion after injury.